CLINICAL DECISIONS

Early Administration of Antibiotics for Suspected Sepsis

Michael Y. Mi, Michael Klompas, Laura Evans

N Engl J Med 2019; 380:593-596
DOI: 10.1056/NEJMclde1809210

Case Vigenette 病例

A Man with Hypoxemia and a Woman with Acute Kidney Injury

一名低氧血症男性患者及一名急性肾损伤女性患者

Michael Y. Mi, M.D.

Mr. Shui is a 35-year-old man who is brought to the emergency department by ambulance after falling from the crest of a tall wave while surfing. He had been in the water for approximately 10 minutes before a lifeguard reached him and brought him to shore. At that time, he was unconscious and coughing and had a palpable pulse. A friend accompanied him to the nearest community hospital, where you work. The friend thinks that Mr. Shui is generally in good health and takes no medications regularly, but earlier in the day, Mr. Shui mentioned to his friend that he had felt slightly fatigued and had had a persistent cough for 2 days. He drinks alcohol occasionally. He does not smoke tobacco but smokes marijuana regularly.

Shui先生是一名35岁男性患者，因冲浪时从浪峰处摔落被救护车送到急诊。救生员找到患者并将其带至岸边前，患者已在水中约10分钟。那时，患者意识丧失，咳嗽，脉搏可扪及。他的朋友跟他一起在你所工作的最近的社区医院就诊。朋友表示，Shui先生平时身体健康，并未长期服药，但出事当天早上，患者曾提到自己感觉轻度乏力，咳嗽已持续2天。患者偶尔饮酒，不吸烟，但经常吸食大麻。

On examination, his temperature is 36.0°C, blood pressure 98/65 mm Hg, heart rate 110 beats per minute, respiratory rate 24 breaths per minute, and oxygen saturation 90% while he is breathing ambient air. He opens his eyes and moves his limbs in response to commands but is confused and disoriented. Breath sounds are diminished at the base of both lungs. There is a 3-cm laceration on the right side of his scalp. The remainder of the physical examination is unremarkable. The complete blood count is notable for a white-cell count of 12,400 per cubic millimeter. Electrolyte levels, renal function, and liver-function tests are within normal limits. Arterial blood gas analysis reveals a pH of 7.37, partial pressure of oxygen (Po₂) of 60 mm Hg, partial pressure of carbon dioxide (Pco₂) of 36 mm Hg, and lactate level of 2.2 mmol per liter. A chest radiograph shows bibasilar air-space opacities. Computed tomography (CT) of the head and neck without administration of contrast material shows no acute intracranial abnormalities and no fractures of the cervical spine.

体格检查发现，体温36.0°C，血压98/65 mm Hg，心率110 bpm，呼吸频率24 bpm，吸空气时氧饱和度90%。患者可遵嘱睁眼及活动肢体，但意识模糊，定向力障碍。双肺底呼吸音减低。右侧头皮有3-cm裂伤。其余体格检查没有异常发现。血常规检查白细胞计数12,400/mL。电解质、肾功能及肝功能检查均正常。动脉血气分析pH 7.37，Po₂ 60 mm Hg，Pco₂ 36 mm Hg，乳酸水平2.2 mmol/L。胸片显示双侧肺底实变。头颅及颈部CT平扫未发现急性颅内异常，颈椎未见骨折。

Ms. Wilkinson is a 72-year-old woman with a history of hypertension and urgency urinary incontinence who presents to the emergency department with a 1-day history of acute-onset abdominal pain in the left lower quadrant. Before the onset of abdominal pain, she had had constipation for 3 days and had not urinated for 1 day despite her efforts to drink plenty of water. She takes extended-release oxybutynin, at a dose of 30 mg daily, and she was recently given a prescription for hydrochlorothiazide, 25 mg daily. She does not smoke or drink alcohol.

Wilkinson女士是一名72岁女性患者，有高血压及尿潴留病史。患者因急性起病的左下腹疼痛1天到急诊就诊。在腹痛发生前，患者便秘3天，尽管大量饮水，但一整天未排尿。患者服用缓释奥西布宁30 mg qd，近期开始服用双氢克尿塞25 mg qd。患者不吸烟也不饮酒。

Her temperature is 36.7°C, blood pressure 126/75 mm Hg, heart rate 100 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 99% while she is breathing ambient air. On examination, she has tenderness to palpation of the left lower quadrant of the abdomen. She is alert and fully oriented. Cardiac and pulmonary examinations are normal. Laboratory studies show a creatinine level of 2.0 mg per deciliter (180 μmol per liter), anion gap 21 mmol per liter, white-cell count 24,200 per cubic millimeter with a predominance of neutrophils, hematocrit 45.0%, and lactate 3.9 mmol per liter. CT of the abdomen and pelvis with administration of contrast material shows large stool volume in the descending and sigmoid colon without evidence of gastrointestinal wall edema or hypoenhancement. A chest radiograph shows clear lungs without focal consolidations. An indwelling urinary catheter is placed, and 1 liter of urine is drained. Results of urinalysis are within normal limits.

患者体温 36.7°C，血压126/75 mm Hg，心率100 bpm，呼吸频率18 bpm，吸空气时氧饱和度99%。体格检查发现，触诊左下腹时有压痛。患者意识清楚，定向力正常。心肺检查正常。实验室检查发现肌酐2.0 mg/dL (180 μmol/L)，阴离子间隙21 mmol/L，白细胞计数24,200/mL，中性粒细胞为主，血球压积45.0%，乳酸3.9 mmol/L。腹部及盆腔增强CT显示降结肠及乙状结肠内大量粪便，没有胃肠道水肿或低密度表现。胸片显示肺部正常，未见局灶实变。患者留置尿管，引流尿液1 L。尿常规检查结果正常。

You are the on-call provider caring for both Mr. Shui and Ms. Wilkinson. You suspect that there may be infections underlying the presentations of both patients, but you are not certain. You believe that early administration of antibiotics to patients with sepsis may save lives, but antibiotics can have serious adverse effects. Your task is to decide whether to administer antibiotics in addition to providing supportive care.

你负责上述两名患者的诊治。你怀疑两名患者的基础病因均可能为感染，但并不确定。你相信早期使用抗生素可能挽救脓毒症患者生命，但抗生素也可以导致严重不良反应。除支持治疗外，你的任务是确定是否应当使用抗生素。

1. Do not administer antibiotics. 不应使用抗生素
2. Administer antibiotics immediately. 立即使用抗生素

Option 2 选项2

Administer Antibiotics Immediately 立即使用抗生素

Laura Evans, M.D.

Both Mr. Shui and Ms. Wilkinson have presented for medical care with signs and symptoms that arouse concern for sepsis; however other explanations are also possible. Thus, the question in these cases is about the diagnostic certainty required to begin therapy — specifically, the potential risks of withholding therapy as compared with the risk of the therapy itself.

Shui先生和Wilkinson女士就诊时的症状体征均提示存在脓毒症；然而，也可能存在其他原因。因此，这两个病例的问题在于开始治疗需要何种诊断确定性—特别需要权衡不进行治疗的可能风险与治疗本身的风险。

Sepsis is defined by Sepsis-3 as “life-threatening organ dysfunction caused by a dysregulated host response to infection.”¹ In patients with sepsis, timely initiation of antimicrobial therapy is a cornerstone of treatment. To break the decision down, there are two steps the clinician must take: decide whether infection is present or suspected and assess whether the patient has acute organ dysfunction attributable to the known or suspected infection. I will address both steps in each case.

根据sepsis-3定义，脓毒症是感染引起的宿主反应失调导致的致命性器官功能障碍。对于脓毒症患者，及时开始抗生素治疗是治疗的关键。为做出临床决策，临床医生应当完成以下两个步骤：确定是否存在明确或可疑的感染，评估患者是否存在已知或可疑感染导致的急性器官功能障碍。我将根据每个病例的情况分别讨论这两个问题。

Whether infection is present is unclear from the presentation of each patient, although it is reasonable to suspect infection in both patients. Mr. Shui had been fatigued and had had a cough for 2 days before his presentation. He has borderline hypothermia and hypotension, tachycardia, tachypnea, and hypoxemia with a mild elevation of his white-cell count, and he has decreased breath sounds at the lung bases and bibasilar opacities. Aspiration without infection is certainly an alternative explanation in the context of a nonfatal drowning event, but infection cannot be ruled out at this stage. Similarly, Ms. Wilkinson presents with abdominal pain, urinary retention while she is taking an antispasmodic agent, and a markedly elevated white-cell count. Despite the negative urinalysis, infection cannot be fully ruled out at this time.

根据每名患者的临床表现，是否存在感染尚不清楚，尽管怀疑感染是合理的。Shui先生就诊前乏力及咳嗽病史已有2天。患者出现轻度低体温及低血压、心动过速、呼吸频数、低氧血症伴白细胞轻度升高。患者肺底呼吸音减低，且出现双肺底透光度降低。在发生非致命性溺水的情况下，误吸而没有感染显然是另一种可能，但目前并不能排除感染。与此相似，Wilkinson女士因服用止痉挛药物期间腹痛、尿潴留及白细胞计数显著升高就诊。尽管尿常规检查结果为阴性，但此时无法完全排除感染。

Regarding step two, the Sepsis-3 definition suggests the use of the SOFA score to assess for organ dysfunction, whereas previous definitions used slightly different criteria.^1,10,11Mr. Shui has hypoxemia and altered mental status. Ms. Wilkinson has acute kidney injury and a creatinine level of 2.0 mg per deciliter. Both patients have elevated lactate levels, which is commonly used as a biomarker of end-organ dysfunction in sepsis even though the lactate level is not included in the SOFA score.^10,11

至于第二步，sepsis-3定义提示使用SOFA评分评价器官功能障碍，而既往的定义采用不同的诊断标准。Shui先生有低氧血症和意识障碍。Wilkinson女士发生急性肾损伤，肌酐水平2.0 mg/dL。两名患者均有乳酸水平升高，后者常作为脓毒症时终末器官功能障碍的生物标志物，尽管并未包括在SOFA评分中。

The Surviving Sepsis Campaign guidelines strongly recommend initiation of intravenous antimicrobial agents within 1 hour or, if possible, even sooner, both in patients with sepsis and in patients with septic shock.¹² Published data corroborate the studies that were used to inform the guideline recommendation, with the data showing a 4-to-7% increase in the odds ratio for death for each hour delay in the initiation of antimicrobial therapy.^6,13

对于脓毒症及感染性休克患者而言，挽救脓毒症行动指南强烈推荐在一小时内静脉使用抗生素，如有可能应当更早。发表的资料也支持用于做出指南推荐意见的研究结果，即抗生素治疗每延误一个小时，患者死亡的风险增加4-7%。

Both Mr. Shui and Ms. Wilkinson have possible infection, and both patients have definite signs of acute organ dysfunction. The potential risk of withholding therapy is high in both patients, whereas the risk of prompt and appropriate antibiotic therapy until more information is available is low. I would give both patients an initial dose of antibiotics while continuing to evaluate for infection. That said, a commitment to antimicrobial stewardship is essential. If further investigations are negative for infection, de-escalation or discontinuation of unnecessary antimicrobial agents is critical to reduce the risk of antibiotic-associated adverse drug effects and antimicrobial resistance.¹⁴

Shui先生和Wilkinson女士都可能存在感染，且均有明确的急性器官功能障碍表现。因此，对于这两名患者而言，不进行抗生素治疗的可能风险极大，而立即开始适当的抗生素治疗，等待更多检查结果的风险较低。对于这两名患者，我会给予一剂抗生素，同时继续对感染诊断进行评估。换言之，对使用抗生素的合理管理非常关键。如果进一步检查不支持感染，则降阶梯或停用不必要的抗生素对于减少抗生素相关不良事件及抗生素耐药的风险非常重要。